Methods:

In the 6-mo DB study, 170 PsA pts previously exposed to DMARDs, including anti-TNF agents, were randomized (1:1:1:1) to receive placebo (PBO) or ABA 30/10 (2 initial doses of 30 mg/kg, followed by 10 mg/kg), 10 or 3 mg/kg on Days 1, 15, 29, and once every 28 days thereafter. Pts who completed this phase were eligible to continue in an OL study, and received ABA 10 mg/kg every 28 days for at least 6 mos. Endpoints included measures of joint disease (ACR20, DAS28), joint inflammation by magnetic resonance imaging (MRI), skin disease (target lesion [TL] score, Psoriasis Area and Severity Index [PASI]), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and safety. Data were as-observed and analyzed on a modified intent-to-treat basis.

Results:

A total of 147 pts from all 4 DB treatment groups entered the OL phase; baseline characteristics were similar among groups except for more pts being previously exposed to anti-TNF agents in the 30/10 mg/kg group (49%) than other groups (2437%). Eighty-eight pts were still on treatment with 47 pts discontinuing due to lack of efficacy. Efficacy data are presented by original randomization group [Table 1]. At Day 169 of DB treatment, ABA improved ACR20 and DAS28, HAQ-DI, TL and PASI scores, and also resulted in less joint damage by MRI evaluation, as compared to PBO. Improvements in ACR and DAS28, reduction in joint damage by MRI and improvement in HAQ-DI continued through Day 365 in pts treated with ABA in the OL phase. Improvements in TL and PASI scores also continued through Day 365. Pts on PBO during the DB period achieved comparable improvements in joint and skin disease, joint inflammation and physical function after ABA treatment in the OL phase. Pts treated with ABA 10 mg/kg during the DB period appeared to have achieved the greatest overall improvements. The safety profile during the OL treatment was consistent with that during the DB period. Serious adverse events were numerically higher in the 10 mg/kg group (18%) vs other groups (812%); these were single events with no obvious pattern. One serious infection was reported in each group except for 2 cases in the 10 mg/kg group. There was 1 malignancy, a lentigo maligna, in the 3 mg/kg group. There were no autoimmune events or deaths.

Conclusions:

The efficacy of ABA in pts with PsA, demonstrated during short-term DB treatment, was sustained throughout 6 mos of OL treatment. No new safety issue was detected.

Table 1. Efficacy of ABA in PsA pts at Days 169 (DB) and 365 (OL)

Response

30/10 mg/kg N=37

ABA 10 mg/kg N=34

3 mg/kg N=43

Placebo N=33

ACR20* at Day 169

49 (33, 65)

56 (39, 73)

35 (21, 49)

24 (10, 39)

ACR20* at Day 365

46 (30, 62)

58 (41, 74)

54 (38, 69)

47 (30, 64)

DAS28 (CRP)* at Day 169

60 (44, 75)

56 (39, 73)

42 (26, 57)

21 (7, 35)

DAS28 (CRP)* at Day 365

52 (35, 69)

79 (63, 94)

58 (42, 74)

52 (34, 69)

MRI of joints at Day 169

Erosion

0.9 (3.2)

-0.4 (3.4)

0.8 (2.5)

1.7 (5.1)

Edema

-0.5 (1.6)

-0.8 (3.0)

-0.1 (1.1)

0.6 (3.4)

Synovitis

-0.2 (3.2)

-1.2 (4.0)

0.3 (2.1)

0.4 (3.5)

MRI of joints at Day 365

Erosion

0.5 (2.6)

0.3 (5.1)

0.6 (2.1)

1.2 (3.8)

Edema

-1.1 (2.0)

-1.7 (2.6)

-0.1 (1.4)

-0.5 (2.5)

Synovitis

-1.8 (3.0)

-2.5 (4.4)

-0.6 (2.1)

-0.7 (3.4)

TL response¶* at Day 169

38 (22, 54)

44 (27, 61)

44 (29, 59)

33 (17, 49)

TL response¶* at Day 365

40 (23, 58)

41 (24, 59)

44 (27, 61)

39 (19, 59)

PASI50* at Day 169

42 (20, 64)

40 (915, 65)

45 (23, 67)

19 (0, 38)

PASI50* at Day 365

31 (9, 54)

54 (27, 81)

47 (21, 72)

40 (10, 70)

HAQ§* at Day 169

41 (25, 56)

53 (36, 70)

38 (23, 53)

24 (10, 39)

HAQ§* at Day 365

40 (23, 58)

57 (39, 76)

53 (36, 70)

52 (32, 73)

Treatment groups represent treatment received the DB period. N indicates the number of pts who completed the DB treatment and who received abatacept 10 mg/kg in the OL phase.